In a general nucleotide unit for chemically synthesizing a RNA oligonucleotide, the 2′-hydroxy group is protected, 3′-hydroxy group is substituted by the group for elongating a phosphate bond and 5′-hydroxy group is protected. For example, in a phosphoramidite method, which is most commonly used at the present days among chemically synthesizing methods of oligonucleotide, a nucleotide which is protected at 2′-hydroxy group and 5′-hydroxy group by respectively different substituents and has a 2-cyanoethoxydiisopropylphosphoramidite group at 3′-hydroxy group is used. It is needed for synthesizing such a nucleotide to discriminate the hydroxy groups at the 2′-, 3′- and 5′-positions, and introduce a protecting group or substituent suitable for each hydroxy groups.
The following method has been known as the method for introducing different substituents to 2′-hydroxy group and 3′-hydroxy group, both of which are secondary hydroxy groups.
(1) After 3′-hydroxy group and 5′-hydroxy group are protected with cross-linked silyl groups and the like, 2′-hydroxy group is protected with a suitable group. Next, the cross-linked silyl groups are removed, 5′-hydroxy group is protected, and then a substituent for elongating an intended phosphate bond is introduced to 3′-hydroxy group (Non-patent Document 1).
In addition, the following methods have been known as the method for directly protecting 2′-hydroxy group or 3′-hydroxy group of a nucleoside derivative of which 2′,3′-hydroxy groups are not protected.
(2) Tert-butyldimethylsilylchloride is reacted in the presence of silver nitrate or a base (Non-patent Documents 2 and 3).
(3) Phenyl isocyanate is reacted in the presence of a base or a tin oxide (Non-patent Documents 4, 5 and 6).
    Non-patent Document 1: TETRAHEDRON LETTERS, 2002, 43, 1983    Non-patent Document 2: CANADIAN JOURNAL OF CHEMISTRY, 1982, 1106    Non-patent Document 3: TETRAHEDRON LETTERS, 1981, 22, 4775    Non-patent Document 4: NUCLEIC ACIDS RESEARCH SYMPOSIUM SERIES, 1981, 10, 33    Non-patent Document 5: NUCLEIC ACIDS RESEARCH SYMPOSIUM SERIES, 1979, 6, S37    Non-patent Document 6: HETEROCYCLES, 1979, 13, 181